SQZ^® eAPC Platform Demonstrates that mRNA-based Expression of Co-Stimulatory CD86 and Membrane-bound IL-2 and IL-12 Dramatically Increases Antigen-Specific CD8 T Cell Activity

T Cell Responses Shown Across Multiple Antigens In Vitro and In Vivo Using mRNAs that Encode Infectious Disease or Tumor-Related Antigens, including HPV (E6 and E7) and KRAS

Beyond eAPC Preclinical Advances, a SQZ AAC Phase 1/2 Clinical Trial in Progress Presentation to be Delivered on April 13

Data Presented at the American Association for Cancer Research 2022 Annual Meeting

SQZ Biotechnologies (NYSE: SQZ), focused on unlocking the full potential of cell therapies for multiple therapeutic areas, today shared enhanced antigen presenting cell (eAPC) preclinical data demonstrating that delivery of multiple mRNAs encoding for disease-specific antigens together with immune stimulators (CD86 costimulatory factor and membrane bound IL-2 and IL-12 cytokines) had a synergistic effect that substantially increased killer T cells in humanized mouse models. The preclinical data, presented at the American Association for Cancer Research (AACR) 2022 Annual Meeting, showed this in vivo enhancement can be seen with a variety of disease antigen mRNAs across a range of HLA types. The findings indicate the potential of the company’s eAPC platform to induce a robust killer T cell response against specific diseases, and the opportunity to increase the number of patients who could potentially benefit from eAPC therapeutic candidates.

The company’s first eAPC therapeutic candidate, SQZ-eAPC-HPV, is in a Phase 1/2 clinical trial (COMMANDER-001) in patients who have human papillomavirus positive (HPV16+) solid tumors. SQZ-eAPC-HPV delivers mRNA for HPV-specific E6 and E7 antigens, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines. This new platform represents sophisticated engineering that we believe to be an advancement over the company’s APC platform candidate, which has demonstrated promising preliminary monotherapy clinical activity in a patient with HPV16+ solid tumors.

“Our eAPC preclinical data, both in vitro and in vivo, demonstrate the synergistic potential of our multiple mRNA delivery approach on activating CD8+T cells,” said Howard Bernstein, M.D., Ph.D., Chief Scientific Officer at SQZ Biotechnologies. “The inclusion of disease-specific antigens, costimulatory factor, and cytokines into a single cell therapy offers tremendous opportunity for patient impact. With the capability to engineer all three T cell activating signals simultaneously, we can pursue additional preclinical activities that could extend our eAPC platform to additional indications.”

In addition to the eAPC preclinical data, a Trial in Progress poster presentation of the ENVOY-001 Phase 1/2 clinical trial will be delivered by Victoria Villaflor, M.D., City of Hope Medical Center. The presentation will summarize the ENVOY-001 study design of SQZ-AAC-HPV, the company’s first engineered red blood cell clinical candidate being investigated in patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors.

AACR EAPC MRNA HIGHLIGHTS IN HUMANIZED MOUSE MODEL

Synergistic Impact of Multiple mRNA T cell Stimulators

• Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a dramatic increase in killer T cells compared to APCs with mRNA for antigen alone
• Mice treated with human eAPCs including mRNA for influenza (Flu) antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have a three-fold increase in killer T cell compared to APCs with mRNA for antigen alone

Strong T Cell Responses Across Multiple HLA Types

• Mice treated with human eAPCs including mRNA for CMV antigen, CD86 costimulatory factor, and membrane-bound IL-2 and IL-12 cytokines were shown to have higher killer T cells responses across a range of HLA types (A*01, A*02, A*11, A*24, B*07, B*35) compared to those squeezed with CMV peptide alone

AACR mRNA HIGHLIGHTS IN HUMAN PBMCs (B cell, T cell, NK cell, Monocytes)

Expansion of CD8 T Cells & Cytokine Signaling

• Human PBMCs with antigen-encoding mRNA for CMV, Flu, HPV16 E6, HPV16 E7 and KRAS G12V substantially increased activation of antigen-specific T cells in vitro compared to untreated PBMCs
• Membrane-bound IL-2 and IL-12 mRNA delivery in PBMC subsets led to surface expression of the cytokines and functional signaling

AACR eAPC Poster Presentation

Title: Co-delivery of antigen-encoding mRNA and signal 2/3 mRNAs to PBMCs by CellSqueeze^® technology generates SQZ^® eAPCs that prime CD8 T cells in humanized mouse model

Presenter: Scott Loughhead, PhD, SQZ Biotechnologies

Session Date and Time: Tuesday, Apr 12, 2022 9:00 AM - 12:30 PM ET

Poster Board Number: 19

Abstract Number: 2853

AACR Trial in Progress Presentation

Title: ENVOY-001: A phase 1, multicenter, open-label study of SQZ-AAC-HPV as monotherapy and in combination with immune checkpoint inhibitors in HLA-A*02+ patients with HPV16+ recurrent, locally advanced, or metastatic solid tumors

Presenter: Victoria M. Villaflor, MD, City of Hope Medical Center

Session Date and Time: Wednesday, April 13, 2022 9:00 AM - 12:30 PM ET

Poster Section: 35

Abstract Number: 7645

About SQZ-AAC-HPV

SQZ^® Activating Antigen Carriers (AACs), derived from engineered red blood cells (RBCs), are designed to transport tumor-specific antigens and adjuvant to a patient’s own professional antigen presenting cells (APCs). The APCs would then activate CD8 killer T cells that travel to tumor sites and attack specific diseased cells. SQZ-AAC-HPV is the company’s first AAC clinical candidate, and it is being evaluated in a Phase 1/2 clinical trial (ENVOY-001 or SQZ-AAC-HPV-101) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate is being studied as a monotherapy and in combination with immune checkpoint inhibitors.

ENVOY-001 Trial Design

SQZ-AAC-HPV is being evaluated in a Phase 1/2 clinical trial (ENVOY-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with immune checkpoint inhibitors. The study consists of two parts. The first part is designed to assess the safety and tolerability of multiple doses of SQZ-AAC-HPV monotherapy in treatment-experienced patients. The second part of the study will assess safety and tolerability of SQZ-AAC-HPV in combination with nivolumab and/or ipilimumab.

About SQZ-eAPC-HPV

SQZ^® Enhanced Antigen Presenting Cells (eAPC) are derived from peripheral blood mononuclear cells (PBMCs), which are primarily composed of monocytes, T cells, B cells, and NK cells, and engineered with various mRNA encoding for multiple target antigens and immuno-stimulatory signals, including CD86 and membrane-bound IL-2 and IL-12. The company has presented preclinical findings showing that SQZ eAPCs have generated robust T cell responses in human in vitro and in vivo models. Additionally, it was demonstrated that HPV16-encoding mRNA delivery to PBMCs stimulated CD8+ T cells across a range of HLA haplotypes, supporting eAPC clinical development in broader HPV16⁺ patient populations.

COMMANDER-001 Trial Design

SQZ-eAPC-HPV is being evaluated in a Phase 1/2 clinical trial (COMMANDER-001) for the treatment of HPV16+ advanced or metastatic solid tumors. The investigational candidate, which targets E6 and E7 oncoproteins, is being studied as a monotherapy and in combination with pembrolizumab, an immune checkpoint inhibitor. The study consists of two parts. The first part is designed to assess safety and tolerability of multiple doses of SQZ-eAPC-HPV in treatment-experienced patients, following a dose-escalation scheme for monotherapy, and a dose de-escalation for the combination with pembrolizumab. The second part of the study will assess clinical response of SQZ-eAPC-HPV monotherapy in combination with pembrolizumab in immune checkpoint inhibitor treatment-naïve patient populations.

About Human Papillomavirus Positive Cancers

Human papillomavirus (HPV) is one of the most common viruses worldwide and certain strains persist for many years, often leading to cancer. According to the Centers for Disease Control (CDC), in the United States HPV+ tumors represent 3% of all cancers in women and 2% of all cancers in men, resulting in over 39,000 new cases of HPV+ tumors every year. HPV infection is larger outside of the U.S., and according to the International Journal of Cancer, HPV+ tumors account for 4.5% of all cancers worldwide resulting in approximately 630,000 new cases every year. According to the CDC, HPV infection plays a significant role in the formation of more than 90% of anal and cervical cancers, and most cases of vaginal (75%), oropharyngeal (70%), vulval (70%) and penile (60%) cancers.

About SQZ Biotechnologies

SQZ Biotechnologies Company is a clinical-stage biotechnology company focused on unlocking the full potential of cell therapies for patients around the world and has active programs in oncology, autoimmune and infectious diseases, as well as additional exploratory initiatives to support future pipeline growth. The company’s proprietary Cell Squeeze^® technology offers the unique ability to deliver multiple biological materials into many cell types to engineer what we believe can be a broad range of potential therapeutics. With demonstrated production timelines under 24 hours and the opportunity to eliminate preconditioning and lengthy hospital stays, our approach could significantly broaden the therapeutic range and accessibility of cell therapies. The company’s first therapeutic applications seek to generate target-specific immune responses, both in activation for the treatment of solid tumors and infectious diseases, and in immune tolerance for the treatment of autoimmune diseases. For more information, please visit www.sqzbiotech.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements contained that do not relate to matters of historical fact should be considered forward-looking statements, including without limitation statements relating to events and presentations, our platform development, our product candidates, project funding, preclinical and clinical activities, progress and outcomes, development plans, manufacturing, clinical safety and efficacy results, therapeutic potential, market opportunities and disease prevalence. These forward-looking statements are based on management's current expectations. Actual results could differ from those projected in any forward-looking statements due to several risk factors. Such factors include, among others, risks and uncertainties related to our limited operating history; our significant losses incurred since inception and expectation to incur significant additional losses for the foreseeable future; the development of our initial product candidates, upon which our business is highly dependent; the impact of the COVID-19 pandemic on our operations and clinical activities; our need for additional funding and our cash runway; the lengthy, expensive, and uncertain process of clinical drug development, including uncertain outcomes of clinical trials and potential delays in regulatory approval; our ability to maintain our relationships with our third party vendors and strategic collaborators; and protection of our proprietary technology, intellectual property portfolio and the confidentiality of our trade secrets. These and other important factors discussed under the caption "Risk Factors" in our most recent Annual Report on Form 10-K and other filings with the U.S. Securities and Exchange Commission could cause actual results to differ materially from those indicated by the forward-looking statements. Any forward-looking statements represent management's estimates as of this date and we undertake no duty to update these forward-looking statements, whether as a result of new information, the occurrence of current events, or otherwise, unless required by law.

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